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Metal Nanoparticles’ Biological Activity and Pharmaceutical Applications

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A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: 25 December 2024 | Viewed by 23300

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Dr. Elitsa L. Pavlova

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Biophysics and Medical Physics Group, Optics and Spectroscopy Department, Faculty of Physics, Sofia University "St. Kliment Ohridski", 5 James Boucher Blvd., 1164 Sofia, Bulgaria
Interests: biophysics; physiology; cell biology; disease; oxidative stress; reactive oxygen species (ROS); antioxidants; antioxidant enzymes; pharmaceuticals; nanoparticles

Prof. Dr. Debbie Crans

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Department of Chemistry, Colorado State University, Fort Colllins, CO 80523, USA
Interests: biological, bioinorganic, bioorganic and bioanalytical chemistries; drugs for diseases such as tuberculosis, Alzheimer’s diabetes and cancer; organic drugs and transition metal-based drugs; menaquinone, pyrazinamide, metformin, platinum and vanadium derivatives; lipid systems and micro-emulsion environments
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Dear Colleagues,

Nanoparticles have been the subject of numerous studies because of their specific physicochemical characteristics, which make them suitable for introduction and application in living systems. The ability of metal nanoparticles to interact with cells, as well as their structures and cellular metabolites, is of particular importance in their applications as drug carriers, and in the diagnosis and treatment of various diseases. The properties of the nanoparticles depend strongly on their shape, size and material. One of the problems with their practical applications in living organisms is their toxicity.

Usually, two basic approaches are applied in the evaluation of the harmful effects of the nanoparticles prepared from metals and other materials—the measurement of their cytotoxic and/or antibacterial effects.

Compounds with cytotoxic effects often damage the permeability and structure of the cell membrane and/or cell metabolism. Cytotoxicity can be measured using various methods and cell cultures, depending on the focus of the research. One quite informative approach is the registration of the kinetics of the cytotoxic response, instead of the snapshot used in the colorimetric standard endpoint assays.

The evaluation of the antibacterial activity applies traditional microbiological assays to test the safety of the metal nanoparticles against some of the most common Gram-positive and Gram-negative bacteria. These tests are very suitable for establishing a sensitivity scale, especially when testing newly synthesized nanomaterials.

Another set of very informative reactions describing the safety of metal nanomaterials is their redox activity, and especially effects on oxidative stress. Free radical reactions and generation of ROS are vital metabolic responses that ensure the body’s homeostasis, functional activity and adaptation. The speed of these reactions is maintained by a complex system of regulation, and its imbalance is a universal mechanism and cause for the development of acute and chronic diseases.

Let’s dive into the metal nanoworld! I look forward to your valuable contribution with the description of the biological activities and applications of metal nanoparticles, their combinations with natural or synthetic substances or their applications as drug and diagnostic tools!

Dr. Elitsa L. Pavlova
Prof. Dr. Debbie C. Crans
Guest Editors

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Keywords

metal nanoparticles
redox reactions
biological activity
pharmaceuticals
cytotoxicity
antibacterial effect
oxidative stress
disease
safety
in vivo applications

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Published Papers (8 papers)

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Research

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23 pages, 45447 KiB

Open AccessArticle

Antimicrobial and Oxidаtive Activities of Different Levels of Silver-Exchanged Zeolites X and ZSM-5 and Their Ecotoxicity

by Elitsa L. Pavlova, Elena P. Nenova, Lyubomira D. Yocheva, Iliana A. Ivanova and Peter A. Georgiev

Pharmaceuticals 2024, 17(12), 1586; https://doi.org/10.3390/ph17121586 - 25 Nov 2024

Viewed by 190

Abstract

Objectives: The antimicrobial, oxidative activities, and ecotoxicity of synthesized silver-loaded zeolites (X and ZSM-5(MFI), Si-to-Al ratios 12 and 25) were studied, linking antimicrobial properties to material structure and released active silver species. Methods: The materials were characterized by SEM, EDX, TEM, and XRPD. All materials, with a silver content of 1–3% wt for the Ss and about 35% wt for the X-zeolites, were tested against Escherichia coli and Staphylococcus aureus. Redox activity was studied in physiological (pH 7.4/37 °C) and optimal (pH 8.5/37 °C) conditions in chemiluminescent model systems. In the ecotoxicity tests, we used Daphnia magna. Results: A proportional correlation was observed between the bactericidal effect of and the silver content in the zeolites. AgX with a Si/Al ratio of ~1.23 and 35% silver showed a higher antimicrobial efficiency, particularly against Gram-negative E. coli versus Gram-positive S. aureus. The concentration thresholds were as follows: AgXas had a bactericidal effect at 0.003 g/L⁻¹, with an MIC at 0.0015 m/L⁻¹ for E. coli; SA25-Ag, AgXcl, AgXrc had a bactericidal effect at 2.5 g/L⁻¹. The bacteria were more resilient than Daphnia magna, which showed a 90–100% lethality at Ag–zeolite concentrations of 0.00625 to 0.0125 g/L⁻¹. AgXas and AgXrc demonstrated strong reactive oxygen species generation at both the physiological and optimal pH, explaining their bactericidal effects. In general, the tested materials showed an inhibition of the generated reactive oxygen species depending on the model system and conditions. Conclusions: The silver species leached from the new materials explain their higher oxidation and bactericidal activity. While suitable for stringently controlled biological applications, their release into the environment, in concentrations higher than 0.01g/L⁻¹, should be avoided. Full article

(This article belongs to the Special Issue Metal Nanoparticles’ Biological Activity and Pharmaceutical Applications)

15 pages, 7531 KiB

Open AccessArticle

Synthesis, Characterization, and Evaluation of the Antimicrobial and Anticancer Activities of Zinc Oxide and Aluminum-Doped Zinc Oxide Nanocomposites

by Muhammad Asif, Muhammad Fakhar-e-Alam, Muhammad Tahir, Farah Jamil, Hassan Sardar, Javed Rehman and Kholood A. Dahlous

Pharmaceuticals 2024, 17(9), 1216; https://doi.org/10.3390/ph17091216 - 16 Sep 2024

Viewed by 974

Abstract

In this research, we developed undoped and aluminum-doped zinc oxide for antimicrobial and anticancer activities. This study focuses on the synthesis, characterization, and biological activities of zinc oxide nanoparticles (ZnO NPs) and aluminum-doped zinc oxide nanocomposites (Zn_1−xAl_xO NCs) at varying concentrations (x = 0, 0.25, 0.5, and 0.75 wt%) using the coprecipitation method. Various characterization techniques such as XRD, UV-Vis, FTIR, EDX, and SEM were performed to analyze the crystal structure, optical properties, functional group identification, elemental composition, and surface morphology. The antimicrobial activity test showed that Zn_0.75Al_0.25O NCs exhibited the strongest inhibition zone against Bacillus cereus compared to Staphylococcus aureus > Pasteurella multocida > Escherichia coli. Moreover, the cytotoxicity and cell viability of liver cancer (HepG-2), breast cancer (MCF-7), ovarian cancer (SKOV3), and normal liver cell lines) were evaluated using the MTT assay, demonstrating that Zn_0.75Al_0.25O NCs not only enhance cell destruction but also show low cytotoxicity and high biocompatibility at low concentrations. These results suggest that Zn_0.75Al_0.25O NCs could be a promising candidate for in vivo anticancer applications and should be further investigated. Full article

(This article belongs to the Special Issue Metal Nanoparticles’ Biological Activity and Pharmaceutical Applications)

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25 pages, 8017 KiB

Open AccessArticle

Development of CuO Nanoparticles from the Mucus of Garden Snail Cornu aspersum as New Antimicrobial Agents

by Pavlina Dolashka, Karina Marinova, Petar Petrov, Ventsislava Petrova, Bogdan Ranguelov, Stella Atanasova-Vladimirova, Dimitar Kaynarov, Ivanka Stoycheva, Emiliya Pisareva, Anna Tomova, Angelina Kosateva, Lyudmila Velkova and Aleksandar Dolashki

Pharmaceuticals 2024, 17(4), 506; https://doi.org/10.3390/ph17040506 - 15 Apr 2024

Cited by 1 | Viewed by 1899

Abstract

Several biologically active compounds involved in the green synthesis of silver and gold nanoparticles have been isolated from snail mucus and characterized. This paper presents a successful method for the application of snail mucus from Cornu aspersum as a bioreducing agent of copper sulfate and as a biostabilizer of the copper oxide nanoparticles (CuONPs-Muc) obtained. The synthesis at room temperature and neutral pH yielded nanoparticles with a spherical shape and an average diameter of 150 nm. The structure and properties of CuONPs-Muc were characterized using various methods and techniques, such as ultraviolet–visible spectroscopy (UV–vis), high-performance liquid chromatography (HPLC), one-dimensional polyacrylamide gel electrophoresis (1D-PAGE), up-conversion infrared spectroscopy Fourier transform (FTIR), scanning electron microscopy combined with energy dispersive spectroscopy (SEM/EDS), Raman spectroscopy and imaging, thermogravimetric analysis (TG-DSC), etc. Mucus proteins with molecular weights of 30.691 kDa and 26.549 kDa were identified, which are involved in the biogenic production of CuONPs-Muc. The macromolecular shell of proteins formed around the copper ions contributes to a higher efficiency of the synthesized CuONPs-Muc in inhibiting the bacterial growth of several Gram-positive (Bacillus subtilis NBIMCC2353, Bacillus spizizenii ATCC 6633, Staphylococcus aureus ATCC 6538, Listeria innocua NBIMCC8755) and Gram-negative (Escherichia coli ATCC8739, Salmonella enteitidis NBIMCC8691, Salmonella typhimurium ATCC 14028, Stenotrophomonas maltophilia ATCC 17666) bacteria compared to baseline mucus. The bioorganic synthesis of snail mucus presented here provides CuONPs-Muc with a highly pronounced antimicrobial effect. These results will expand knowledge in the field of natural nanomaterials and their role in emerging dosage forms. Full article

(This article belongs to the Special Issue Metal Nanoparticles’ Biological Activity and Pharmaceutical Applications)

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15 pages, 2965 KiB

Open AccessArticle

Synthesis, Characterization, and Toxicity Assessment of Zinc Oxide-Doped Manganese Oxide Nanoparticles in a Macrophage Model

by Nasser B. Alsaleh, Anas M. Aljarbou, Mohamed E. Assal, Mohammed A. Assiri, Mohammed M. Almutairi, Homood M. As Sobeai, Ali A. Alshamrani, Sultan Almudimeegh, Mohammad R. Hatshan and Syed F. Adil

Pharmaceuticals 2024, 17(2), 168; https://doi.org/10.3390/ph17020168 - 29 Jan 2024

Cited by 1 | Viewed by 1780

Abstract

The doping of engineered nanomaterials (ENMs) is a key tool for manipulating the properties of ENMs (e.g., electromagnetic, optical, etc.) for different therapeutic applications. However, adverse health outcomes and the cellular biointeraction of doped ENMs, compared to undoped counterparts, are not fully understood. Previously, we have shown that doping manganese oxide nanoparticles with ZnO (ZnO-MnO₂ NPs) improved their catalytic properties. In this study, we assessed the toxicity of ZnO-MnO₂ NPs in Raw 264.7 cells. NPs were prepared via an eco-friendly, co-precipitation method and characterized by several techniques, including transmission and scanning electron microscopy, X-ray diffraction, and Fourier transform infrared. The physicochemical properties of ZnO-MnO₂ NPs, including size, morphology, and crystalline structure, were almost identical to MnO₂ NPs. However, ZnO-MnO₂ NPs showed slightly larger particle aggregates and negative charge in cell culture media. Exposure to ZnO-MnO₂ NPs resulted in lower toxicity based on the cell viability and functional assay (phagocytosis) data. Exposure to both NPs resulted in the activation of the cell inflammatory response and the generation of reactive oxygen species (ROS). Despite this, exposure to ZnO-MnO₂ NPs was associated with a lower toxicity profile, and it resulted in a higher ROS burst and the activation of the cell antioxidant system, hence indicating that MnO₂ NP-induced toxicity is potentially mediated via other ROS-independent pathways. Furthermore, the cellular internalization of ZnO-MnO₂ NPs was lower compared to MnO₂ NPs, and this could explain the lower extent of toxicity of ZnO-MnO₂ NPs and suggests Zn-driven ROS generation. Together, the findings of this report suggest that ZnO (1%) doping impacts cellular biointeraction and the consequent toxicological outcomes of MnO₂ NPs in Raw 264.7 cells. Full article

(This article belongs to the Special Issue Metal Nanoparticles’ Biological Activity and Pharmaceutical Applications)

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20 pages, 4586 KiB

Open AccessArticle

Green Synthesis and Characterization of Silver Nanoparticles Using Azadirachta indica Seeds Extract: In Vitro and In Vivo Evaluation of Anti-Diabetic Activity

by Gauhar Rehman, Muhammad Umar, Nasrullah Shah, Muhammad Hamayun, Abid Ali, Waliullah Khan, Arif Khan, Sajjad Ahmad, Abdulwahed Fahad Alrefaei, Mikhlid H. Almutairi, Yong-Sun Moon and Sajid Ali

Pharmaceuticals 2023, 16(12), 1677; https://doi.org/10.3390/ph16121677 - 1 Dec 2023

Cited by 9 | Viewed by 3194

Abstract

Background: Diabetes mellitus (DM) is a non-communicable, life-threatening syndrome that is present all over the world. The use of eco-friendly, cost-effective, and green-synthesised nanoparticles as a medicinal therapy in the treatment of DM is an attractive option. Objective: In the present study, silver nanoparticles (AI-AgNPs) were biosynthesized through the green synthesis method using Azadirachta indica seed extract to evaluate their anti-diabetic potentials. Methods: These nanoparticles were characterized by using UV-visible spectroscopy, Fourier transform infrared spectrophotometers (FTIR), scanning electron microscopy (SEM), DLS, and X-ray diffraction (XRD). The biosynthesized AI-AgNPs and crude extracts of Azadirachta indica seeds were evaluated for anti-diabetic potentials using glucose adsorption assays, glucose uptake by yeast cells assays, and alpha-amylase inhibitory assays. Results: Al-AgNPs showed the highest activity (75 ± 1.528%), while crude extract showed (63 ± 2.5%) glucose uptake by yeast at 80 µg/mL. In the glucose adsorption assay, the highest activity of Al-AgNPs was 10.65 ± 1.58%, while crude extract showed 8.32 ± 0.258% at 30 mM, whereas in the alpha-amylase assay, Al-AgNPs exhibited the maximum activity of 73.85 ± 1.114% and crude extract 65.85 ± 2.101% at 100 µg/mL. The assay results of AI-AgNPs and crude showed substantial dose-dependent activities. Further, anti-diabetic potentials were also investigated in streptozotocin-induced diabetic mice. Mice were administered with AI-AgNPs (10 to 40 mg/kg b.w) for 30 days. Conclusions: The results showed a considerable drop in blood sugar levels, including pancreatic and liver cell regeneration, demonstrating that AI-AgNPs have strong anti-diabetic potential. Full article

(This article belongs to the Special Issue Metal Nanoparticles’ Biological Activity and Pharmaceutical Applications)

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16 pages, 3014 KiB

Open AccessArticle

Process Optimization for the Bioinspired Synthesis of Gold Nanoparticles Using Cordyceps militaris, Its Characterization, and Assessment of Enhanced Therapeutic Efficacy

by Girish Gawas, Muniappan Ayyanar, Nilambari Gurav, Dinesh Hase, Vaishali Murade, Sameer Nadaf, Mohd Shahnawaz Khan, Rupesh Chikhale, Mohan Kalaskar and Shailendra Gurav

Pharmaceuticals 2023, 16(9), 1311; https://doi.org/10.3390/ph16091311 - 16 Sep 2023

Cited by 10 | Viewed by 1785

Abstract

The promising therapeutic implications of nanoparticles have spurred their development for biomedical applications. An eco-friendly methodology synthesizes gold nanoparticles using Cordyceps militaris, an edible mushroom (Cord-Au-NPs), using a quality-by-design approach (central composite design). UV-visible spectroscopy analysis revealed an absorption peak at 540–550 nm, thus confirming the synthesis of gold nanoparticles. Cord-Au-NPs have a crystalline structure, as evidenced by the diffraction peaks. The zeta potential value of −19.42 mV signifies the stability of Cord-Au-NPs. XRD study shows gold facets and EDX analysis revealed a strong peak of spherical nanoparticles in the gold region with a mean particle size of 7.18 nm and a polydispersity index of 0.096. The obtained peaks are closely associated with phenolic groups, lipids, and proteins, as examined by FTIR, suggesting that they function as the reducing agent. Cord-Au-NPs exhibited dose-dependent antioxidant, antidiabetic, and antibacterial activity. The method is eco-friendly, nontoxic, less time-consuming, and does not use synthetic materials, leading to higher capabilities in biomedical applications. Full article

(This article belongs to the Special Issue Metal Nanoparticles’ Biological Activity and Pharmaceutical Applications)

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25 pages, 3834 KiB

Open AccessArticle

In Vitro, Oral Acute, and Repeated 28-Day Oral Dose Toxicity of a Mixed-Valence Polyoxovanadate Cluster

by Mariana de M. Barbosa, Lidiane M. A. de Lima, Widarlane A. da S. Alves, Eucilene K. B. de Lima, Luzia A. da Silva, Thiago D. da Silva, Kahoana Postal, Mohammad Ramadan, Kateryna Kostenkova, Dayane A. Gomes, Giovana G. Nunes, Michelly C. Pereira, Wagner E. da Silva, Mônica F. Belian, Debbie C. Crans and Eduardo C. Lira

Pharmaceuticals 2023, 16(9), 1232; https://doi.org/10.3390/ph16091232 - 30 Aug 2023

Cited by 2 | Viewed by 1542

Abstract

Polyoxovanadates (POV) are a subgroup of polyoxometalates (POM), which are nanosized clusters with reported biological activities. This manuscript describes the first toxicity evaluation of a mixed-valence polyoxovanadate, pentadecavanadate, (Me₄N)₆[V₁₅O₃₆Cl], abbreviated as V₁₅. Cytotoxicity experiments using peripheral blood mononuclear cells (PBMC), larvae of Artemia salina Leach, and in vivo oral acute and repeated 28-day doses in mice was carried out. The LC₅₀ values in PBMC cells and A. salina were 17.5 ± 5.8 μmol L⁻¹, and 17.9 µg L⁻¹, respectively, which indicates high cytotoxic activity. The toxicity in mice was not observed upon acute exposure in a single dose, however, the V₁₅ repeated 28-day oral administration demonstrated high toxicity using 25 mg/kg, 50 mg/kg and, 300 mg/kg doses. The biochemical and hematological analyses during the 28-day administration of V₁₅ showed significant alteration of the metabolic parameters related to the kidney and liver, suggesting moderate toxicity. The V₁₅ toxicity was attributed to the oxidative stress and lipid peroxidation, once thiobarbituric acid (TBAR) levels significantly increased in both males and females treated with high doses of the POV and also in males treated with a lower dose of the POV. This is the first study reporting a treatment-related mortality in animals acutely administrated with a mixed-valence POV, contrasting with the well-known, less toxic decavanadate. These results document the toxicity of this mixed-valence POV, which may not be suitable for biomedical applications. Full article

(This article belongs to the Special Issue Metal Nanoparticles’ Biological Activity and Pharmaceutical Applications)

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Review

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42 pages, 2855 KiB

Open AccessReview

Current Overview of Metal Nanoparticles’ Synthesis, Characterization, and Biomedical Applications, with a Focus on Silver and Gold Nanoparticles

by Ana Flavia Burlec, Andreia Corciova, Monica Boev, Denisa Batir-Marin, Cornelia Mircea, Oana Cioanca, Gabriela Danila, Marius Danila, Anca Florentina Bucur and Monica Hancianu

Pharmaceuticals 2023, 16(10), 1410; https://doi.org/10.3390/ph16101410 - 4 Oct 2023

Cited by 47 | Viewed by 10567

Abstract

Metal nanoparticles (NPs) have garnered considerable attention, due to their unique physicochemical properties, that render them promising candidates for various applications in medicine and industry. This article offers a comprehensive overview of the most recent advancements in the manufacturing, characterization, and biomedical utilization of metal NPs, with a primary focus on silver and gold NPs. Their potential as effective anticancer, anti-inflammatory, and antimicrobial agents, drug delivery systems, and imaging agents in the diagnosis and treatment of a variety of disorders is reviewed. Moreover, their translation to therapeutic settings, and the issue of their inclusion in clinical trials, are assessed in light of over 30 clinical investigations that concentrate on administering either silver or gold NPs in conditions ranging from nosocomial infections to different types of cancers. This paper aims not only to examine the biocompatibility of nanomaterials but also to emphasize potential challenges that may limit their safe integration into healthcare practices. More than 100 nanomedicines are currently on the market, which justifies ongoing study into the use of nanomaterials in medicine. Overall, the present review aims to highlight the potential of silver and gold NPs as innovative and effective therapeutics in the field of biomedicine, citing some of their most relevant current applications. Full article

(This article belongs to the Special Issue Metal Nanoparticles’ Biological Activity and Pharmaceutical Applications)

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